Features of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome
The phenotypic spectrum of BBSOAS is broad and variable, but the most well-established characteristics include developmental delay/intellectual disability and visual impairment (including optic nerve atrophy, optic nerve hypoplasia, and cortical visual impairment). Other common features include hypotonia, oromotor dysfunction, morphological changes of brain structures including thinning of the corpus callosum, and autism spectrum disorder. Individuals are also at an elevated risk of seizures, including infantile spasms.
Genotype-phenotype correlations have been proposed, with individuals with mutations in the DBD typically showing a more severe phenotype, and individuals with whole-gene deletions and truncating mutations tending to have moderate to mild symptoms. Individuals with point mutations outside of the DBD most often manifest the mildest phenotype.
BBSOAS is considered a static encephalopathy and has not been shown to be progressive/degenerative.
BBSOAS is an autosomal dominant disorder. The majority of cases are de novo, but familial cases are also known. The chance of unaffected parents with one affected child having a second affected child is less than 3%, while the chance of an affected parent having an affected child is 50%.
Chen, C.-A. et al. The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype–phenotype correlations. Genet. Med. 18, 1143–1150 (2016).
Links For Further Research
Management of BBSOAS
The following tests and therapies are recommended for patients who have been found to have a mutation in the NR2F1 gene:
- Full, dilated eye examination from an ophthalmologist every two years
- Full hearing evaluation every two years
- Comprehensive psychological evaluation for autism:
- ADI-R and ADOS testing performed by a certified clinical psychologist
- A brain MRI, recommended at 40 months or older
- Physical Therapy
- Occupational Therapy
- Speech Therapy
List of Features
- Developmental delay/intellectual disability
- Visual impairment
- Optic nerve atrophy
- Optic nerve hypoplasia
- (and/or) Cortical visual impairment (CVI)
- Oromotor dysfunction
- Thin corpus callosum
- Repetitive behavior
- Autism spectrum disorder
- Seizures, including infantile spasms and febrile seizures
- Hearing impairment
- Mild and inconsistent dysmorphic facial features